Background
In this study, we comprehensively analyzed genes related to ferroptosis and iron metabolism to construct diagnostic and prognostic models and explore the relationship with the immune microenvironment in HCC.
Methods
Integrated analysis, cox regression and the least absolute shrinkage and selection operator (LASSO) method of 104 ferroptosis- and iron metabolism-related genes and HCC-related RNA sequencing were performed to identify HCC-related ferroptosis and iron metabolism genes.
Results
Four genes (ABCB6, FLVCR1, SLC48A1 and SLC7A11) were identified to construct prognostic and diagnostic models. Poorer overall survival (OS) was exhibited in the high-risk group than that in the low-risk group in both the training cohort (P < 0.001, HR = 0.27) and test cohort (P < 0.001, HR = 0.27). The diagnostic models successfully distinguished HCC from normal samples and proliferative nodule samples. Compared with low-risk groups, high-risk groups had higher TMB; higher fractions of macrophages, follicular helper T cells, memory B cells, and neutrophils; and exhibited higher expression of CD83, B7H3, OX40 and CD134L. As an inducer of ferroptosis, erastin inhibited HCC cell proliferation and progression, and it was showed to affect Th17 cell differentiation and IL-17 signaling pathway through bioinformatics analysis, indicating it a potential agent of cancer immunotherapy.
Conclusions
The prognostic and diagnostic models based on the four genes indicated superior diagnostic and predictive performance, indicating new possibilities for individualized treatment of HCC patients.
Graphical abstract
Twenty-seven diterpenes of six chemical classes, including seven new diterpenes (1, 2, 6, 10, 11, 16, and 19), have been isolated from a collection of the brown alga Dictyota plectens from the South China Sea. The structures of the new diterpenes were elucidated by extensive spectroscopic analysis and by comparison with reported data. In the in vitro assays, 9, 12, 14, 16, and 22 showed inhibitory activity against HIV-1 replication with IC50 values of 16.1-30.5 μM, compounds 5, 13, 24, and 26 exhibited anti-H5N1 activity with inhibition rates of 50%-62% at 30.0 μM, and 12 and 24 also showed potent inhibition against LPS-induced NO production with inhibition rates of 90% and 86%, respectively, at 10.0 μM.
Ten new cembrane-based diterpenes, locrassumins A–G (1–7), (–)-laevigatol B (8), (–)-isosarcophine (9), and (–)-7R,8S-dihydroxydeepoxysarcophytoxide (10), were isolated from a South China Sea collection of the soft coral Lobophytum crassum, together with eight known analogues (11–18). The structures of the new compounds were determined by extensive spectroscopic analysis and by comparison with previously reported data. Locrassumin C (3) possesses an unprecedented tetradecahydrobenzo[3,4]cyclobuta[1,2][8]annulene ring system. Compounds 1, 7, 12, 13, and 17 exhibited moderate inhibition against lipopolysaccharide (LPS)-induced nitric oxide (NO) production with IC50 values of 8–24 μM.
Nineteen metabolites with diverse structures, including the rare pyrroloindoline alkaloid verrupyrroloindoline (1), the unprecedented highly fused benzosesquiterpenoid verrubenzospirolactone (2), the new asteriscane-type sesquiterpenoid 10-deoxocapillosanane D (3), and the two new cyclopentenone derivatives (4S*,5S*)-4-hydroxy-5-(hydroxymethyl)-2,3-dimethyl-4-pentylcyclopent-2-en-1-one (4) and (S)-4-hydroxy-5-methylene-2,3-dimethyl-4-pentylcyclopent-2-en-1-one (5), were isolated from a South China Sea collection of the soft coral Sinularia verruca. Eleven previously described marine metabolites (7−15, 18, and 19) were also obtained as well as three new EtOH-adduct artifacts (6, 16, and 17). The structures of the new compounds were elucidated by extensive spectroscopic analysis and by comparison with previously reported data. Compounds 4, 5, and 16 showed protection against the cytopathic effects of HIV-1 infection with EC 50 values of 5.8−34 μM, and 4, 6, and 16 exhibited inhibition against LPS-induced NO production with IC 50 values of 24−28 μM. S oft corals of the genus Sinularia (family Alcyoniidae) are commonly distributed in the tropical coral reef systems of the world and are well known for being a rich source of biologically active secondary metabolites. In the past several decades, more than 50 Sinularia species have been chemically investigated, resulting in the discovery of hundreds of secondary metabolites including sesquiterpenoids, diterpenoids, polyhydroxylated steroids, cyclopentenones, and butenolides.
Four new xenicanes, namely 4α-hydroxyisodictyohemiacetal (1), 4α-hydroxyisodictyoacetal (2), 13,18-diacetoxy-4-hydroxyisodictyo-19-al (3), and 4α-hydroxypachylactone (8), were isolated from a Chinese collection of the brown alga Dictyota plectens, along with four known analogues (4-7). The structures of the new diterpenes were determined by extensive spectroscopic data analysis. All compounds were evaluated for their antiviral activities against human immunodeficiency virus type 1 (HIV-1) and the highly pathogenic avian influenza A (H5N1) virus, and inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) production in mouse peritoneal macrophages (PEMΦ).
Objectives: To investigate potential diagnostic model for predicting benign or malignant status of subcentimeter pulmonary ground-glass nodules (SPGGNs) (≤1 cm) based on CT texture analysis. Methods: A total of 89 SPGGNs from 89 patients were included; 51 patients were diagnosed with adenocarcinoma, and 38 were diagnosed with inflamed or infected benign SPGGNs. Analysis Kit software was used to manually delineate the volume of interest of lesions and extract a total of 396 quantitative texture parameters. The statistical analysis was performed using R software. The SPGGNs were randomly divided into a training set (n = 59) and a validation set (n = 30). All pre-normalized (Z-score) feature values were subjected to dimension reduction using the LASSO algorithm,and the most useful features in the training set were selected. The selected imaging features were then combined into a Rad-score, which was further assessed by ROC curve analysis in the training and validation sets. Results: Four characteristic parameters (ClusterShade_AllDirection_offset4_SD, ShortRunEmphasis_angle45_offset1, Maximum3DDiameter, SurfaceVolumeRatio) were further selected by LASSO (p < 0.05). As a cluster of imaging biomarkers, the above four parameters were used to form the Rad-score. The AUC for differentiating between benign and malignant SPGGNs in the training set was 0.792 (95% CI: 0.671, 0.913), and the sensitivity and specificity were 86.10 and 65.20%, respectively. The AUC in the validation set was 72.9% (95% CI: 0.545, 0.913), and the sensitivity and specificity were 86.70 and 60%, respectively. Conclusion: The present diagnostic model based on the cluster of imaging biomarkers can preferably distinguish benign and malignant SPGGNs (≤1 cm). Advances in knowledge: Texture analysis based on CT images provide a new and credible technique for accurate identification of subcentimeter pulmonary ground-glass nodules.
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